Targeting the Triple Threat

There's now something to take aim at in triple-negative breast cancer. 

"I’ve basically lived my entire life knowing I was going to get cancer," says Nancy Truesdale, a 42-year-old teacher from Key Largo, Florida. “It was just a matter of when.” Having lost her mother to ovarian cancer and her grandmother to breast cancer, Truesdale knew her cancer risk was high. So she wasn’t surprised when, in July of last year, a routine breast exam revealed a lump in her right breast.  

The biopsy on Truesdale’s tumor revealed triple-negative breast cancer, or TNBC, which means the tumor cells lack expression of three proteins common to various other types of breast cancer—the receptors for the hormones estrogen and progesterone, and a growth factor receptor called HER2.

After surgery to remove the lump (the tumor was found to be stage 2), two 12-week rounds of chemotherapy, a bilateral mastectomy,  a hysterectomy because she’s at high risk for ovarian cancer, and later participation in a clinical trial for Avastin (bevacizumab), Truesdale is cancer-free. “I’ve basically done everything I can do to rid my body of cancer,” she says. “There’s really nothing else I can do but sit and wait.”

Of the roughly 190,000 new cases of breast cancer diagnosed in the U.S. each year, 10 to 20 percent are triple-negative.

The diagnosis of TNBC may be a fearful one, partly because these tumors tend to be aggressive with a high risk of metastasis, and partly because some of the most effective targeted therapies, such as Herceptin (trastuzumab) for HER2-positive breast cancer, and tamoxifen and aromatase inhibitors for hormone receptor-positive breast cancer, don’t work in these patients. As such, the current standard treatment for TNBC has been classic breast cancer chemotherapy, which is particularly effective against TNBC, perhaps because the tumor cells divide rapidly—the hallmark of chemotherapy’s target.

But that standard may soon change. Although TNBC currently lacks its own version of Herceptin, researchers have begun defining TNBC’s unique molecular features in the hope of identifying new targeted drugs. And if recent clinical trial results are any indication, targeted therapies for TNBC are just around the corner.

TNBC, which is more prevalent among premenopausal and African-American women, is a fast-growing cancer that has a higher risk of early recurrence in the first three to five years after diagnosis than do cancers expressing hormone receptors.

Although it’s clear which molecular features triple-negative tumors lack, it’s trickier to define them in concrete terms. “Triple-negative is a bit of a waste-basket terminology,” explains Mark Pegram, MD, an oncologist at the Sylvester Comprehensive Cancer Center in Miami. “The majority of, but not all, triple-negatives are basal tumors,” he says. 

An estimated 65 to 90 percent of triple-negative cancers are basal-like tumors, meaning the cells express proteins typical of basal breast cells (the progenitor cells or stem cells that give rise to mature glandular breast cells), and are associated with a poorer prognosis than non-basal tumors.

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